Spina bifida, a birth defect involving the spinal cord, is common, life-threatening and permanently disabling. Although mandatory folic acid fortification of food supplies has been associated with reductions in the prevalence spina bifida (38% in the United States), spina bifida is far from being eradicated. Consequently, identifying additional interventions to reduce the prevalence of spina bifida remains a public health priority. Maternal weight is a potential target for such an intervention because: (i) the risk of spina bifida has consistently been observed to be increased in the offspring of obese women (BMI > 30 kg/m2), as compared to the offspring of women who fall in the normal BMI category (18.5<BMI<25.0 kg/m); (ii) overweight and obesity are common - present in approximately 50% of women prior to pregnancy and; (iii) weight can be modified. However, as the observed associations are insufficient to establish a causal connection between spina bifida and maternal weight, it is unclear whether pre-pregnancy weight loss will reduce the risk of spina bifida. The lack of strong evidence that maternal weight loss will result in decreased risk of spina bifida is a significant impediment to prevention efforts. The proposed studies will help to establish a causal connection between weight loss and spina bifida and are thus directly responsive to RFA-DD-001, Public Health Research of Modifiable Risk Factors for Spina Bifida. These studies leverage existing data from the Texas Birth Defects Registry (TBDR), which is the largest, active surveillance Registry in the United States. Specifically, a case- control study, using data from the TBDR and Texas vital statistics, will be conducted to evaluate the association between maternal inter-pregnancy change in body mass index and spina bifida. This study will help to establish whether maternal weight change prior to pregnancy is a potential target for reducing the risk of spina bifida. The successful completion of these analyses will fill a major gap in our understanding of the association between maternal weight and spina bifida and will thus provide important direction for future prevention efforts.